title: Variation in MAPT is not a contributing factor to the incomplete penetrance in LHON.
abstract: Leber's hereditary optic neuropathy (LHON) is a common cause of inherited blindness, primarily due to one of three mitochondrial DNA (mtDNA) mutations. LHON, which has an unexplained variable penetrance and pathology, is characterised by disruption of the mitochondrial respiratory chain ultimately resulting in degeneration of the retinal ganglion cells. Phosphorylation of the tau protein is known to cause neurodegeneration and variation in MAPT has been associated with a range of neurodegenerative disorders. Given the relationship between MAPT variation and altered mitochondrial respiratory chain function, we hypothesised that MAPT variation could contribute to the risk of blindness in LHON mtDNA mutation carriers. We studied MAPT variation in a large, well characterised LHON cohort, but were unable to find an association between MAPT genetic variation and visual failure in LHON mtDNA mutation carriers. Our findings suggest that genetic variation in MAPT is unlikely to make a major contribution to the risk of blindness among LHON mutation carriers.
authors.affiliation: Institute for Human Genetics, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: Patrick
authors.initials: P
authors.lastname: Yu-Wai-Man
authors.forename: Philip G
authors.initials: PG
authors.lastname: Griffiths
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D017668:Age of Onset; D001766:Blindness / Q000235:genetics*; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C054369:MAPT protein, human; D016875:tau Proteins